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WO2025056014A1 - Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps - Google Patents

Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps Download PDF

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Publication number
WO2025056014A1
WO2025056014A1 PCT/CN2024/118679 CN2024118679W WO2025056014A1 WO 2025056014 A1 WO2025056014 A1 WO 2025056014A1 CN 2024118679 W CN2024118679 W CN 2024118679W WO 2025056014 A1 WO2025056014 A1 WO 2025056014A1
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Prior art keywords
antibody
antigen
binding fragment
pharmaceutical composition
tim
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PCT/CN2024/118679
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English (en)
Chinese (zh)
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WO2025056014A9 (fr
Inventor
孔令婕
李盈淳
程艳菊
高飞
吴毓昕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chia Tai Tianqing Pharmaceutical Group Co Ltd
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Chia Tai Tianqing Pharmaceutical Group Co Ltd
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Publication of WO2025056014A1 publication Critical patent/WO2025056014A1/fr
Publication of WO2025056014A9 publication Critical patent/WO2025056014A9/fr
Pending legal-status Critical Current
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants

Definitions

  • the present disclosure belongs to the field of biomedicine, and specifically relates to a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof, and uses thereof.
  • PD-1 Programmed death-1 is mainly expressed by activated T lymphocytes and B lymphocytes, and its ligands include PD-L1 and PD-L2.
  • the binding of PD-1 to its ligand will inhibit T cell activation and proliferation, downregulate the secretion of T cell immunostimulatory cytokines, thereby inhibiting T cell immune response and promoting T cell apoptosis.
  • PD-1 is highly expressed on tumor-infiltrating lymphocytes, and its ligand is also upregulated on the surface of a variety of tumor cells. Therefore, anti-PD-1 antibodies can block the immunosuppressive signaling pathway and enhance the body's endogenous anti-tumor immune effect by blocking the binding of PD-1 to its ligand.
  • T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), also known as Hepatitis A Virus Cellular Receptor 2 (HAVCR2), is a member of the TIM family of immunoregulatory proteins.
  • TIM-3 is selectively expressed on the surface of activated Th1 cells, and is also expressed on myeloid cells, DC cells, NK cells, macrophages, and a variety of tumor cells.
  • TIM-3 has a variety of different ligands, including galectin 9, phosphatidylserine (PtdSer), high mobility group protein B1 (HMGB1), and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1).
  • TIM-3 can negatively regulate the body's immune response and avoid damage to the body caused by excessive immune or autoimmune responses.
  • various evidences indicate that TIM-3 protein and/or mRNA is upregulated in a variety of tumor tissues and tumor-associated immune cells, participating in tumor immune escape and immune response, and promoting tumor development.
  • Anti-PD-1 antibodies can be administered in combination with anti-TIM-3 antibodies, but administration of the two antibodies requires multiple administrations at different time points, so a single formulation containing both antibodies will improve patient convenience and reduce drug resistance. Because each antibody has unique physical and chemical properties, such as surface exposed residues, breakable sites, glycosylation sites, deamidation sites, surface charge distribution, isoelectric point, aggregation tendency, solubility, etc., unique formulation excipients are required to maintain the stability of each antibody, making it difficult to determine a single formulation.
  • the present disclosure provides a pharmaceutical composition, wherein the pharmaceutical composition comprises an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof.
  • the second antibody or an antigen-binding fragment thereof is an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the anti-PD-1 antibody or an antigen-binding fragment thereof and the anti-TIM-3 antibody or an antigen-binding fragment thereof are present in the pharmaceutical composition at a fixed dose ratio.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-30, 1:1-20, 1:1-18, 1:1-15, 1:1-12, 1:1-10, 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5.
  • the present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation is obtained by freeze-drying the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides a lyophilized preparation, wherein the lyophilized preparation can form the pharmaceutical composition of the present disclosure after reconstitution.
  • the present disclosure also provides a medicine kit, wherein the medicine kit comprises the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides a vial, wherein the vial comprises the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides a syringe, wherein the syringe comprises the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides an intravenous bag, wherein the intravenous bag comprises the pharmaceutical composition of the present disclosure.
  • the present disclosure also provides a method for preparing the pharmaceutical composition and lyophilized preparation of the present disclosure.
  • the present disclosure also provides a method for treating a disease in a subject, the method comprising administering a pharmaceutical composition or lyophilized formulation of the present disclosure to the subject.
  • the present disclosure also provides a method for treating a disease in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure to the subject.
  • the disease includes cancer and infectious diseases.
  • the present disclosure also provides a method for enhancing the immune response of a subject, the method comprising administering to the subject a pharmaceutical composition or lyophilized formulation of the present disclosure.
  • the present disclosure also provides a method for enhancing the immune response of a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition or lyophilized formulation of the present disclosure.
  • FIG1 shows the ELISA method for detecting the binding of h50B5 to CHO-S-HuTIM-3 cells that highly express human TIM-3;
  • FIG2 shows the promoting effect of h50B5 on IFN- ⁇ secretion in MLR
  • FIG3 shows the blood drug concentration curve of tumor-bearing mice after a single intravenous injection of h50B5 in a subcutaneous transplanted tumor model of lung cancer HCC827 human immune reconstituted mice (PBMC-NCG).
  • buffer means a pharmaceutically acceptable buffer, which refers to a substance that helps maintain the pH of the pharmaceutical composition within a desired pH range.
  • Buffers suitable for use in the present disclosure include phosphate buffers, acetate buffers, citrate buffers, Tris buffers, or histidine buffers. In addition, a mixture of two or more buffers may also be used.
  • the buffer suitable for use in the present disclosure is a histidine buffer.
  • phosphate buffer is a buffer containing phosphate ions.
  • phosphate buffers include sodium phosphate buffers, potassium phosphate buffers, and the like.
  • Sodium phosphate buffers can be prepared using disodium hydrogen phosphate or a hydrate thereof (e.g., disodium hydrogen phosphate dodecahydrate) and sodium dihydrogen phosphate or a hydrate thereof (e.g., sodium dihydrogen phosphate dihydrate).
  • acetate buffer is a buffer containing acetate ions.
  • acetate buffers include potassium acetate buffer, ammonium acetate buffer, sodium acetate buffer, etc.
  • Sodium acetate buffer can be prepared using acetic acid and sodium acetate or a hydrate thereof (e.g., anhydrous sodium acetate or sodium acetate trihydrate).
  • citrate buffer is a buffer containing citrate ions.
  • examples of citrate buffers include sodium citrate buffer, potassium citrate buffer, calcium citrate buffer, etc.
  • Sodium citrate buffer can be prepared using citric acid and sodium citrate or a hydrate thereof (e.g., trisodium citrate dihydrate).
  • histidine buffer is a buffer comprising histidine ions.
  • histidine buffers include histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, histidine-acetate buffer, histidine-phosphate buffer, etc.
  • Histidine-histidine hydrochloride buffer can be prepared using histidine (e.g., L-histidine) and histidine hydrochloride or its hydrate (e.g., monohydrated histidine hydrochloride), or using histidine hydrochloride or its hydrate (e.g., monohydrated histidine hydrochloride).
  • Histidine-hydrochloride buffer can be prepared using histidine (e.g., L-histidine) and further adjusted with hydrochloric acid to pH.
  • Histidine-acetate buffer can be prepared using histidine (e.g., L-histidine) and further adjusted with acetic acid to pH.
  • Histidine-phosphate buffer can be prepared using histidine (e.g., L-histidine) and further adjusted with phosphoric acid to pH.
  • antioxidant refers to a substance that can prevent, slow down or reduce the oxidation of an active ingredient (eg, an antibody) in a pharmaceutical composition.
  • isotonic agent refers to a substance that helps maintain the osmotic pressure of a pharmaceutical composition at or close to the physiological osmotic pressure.
  • excipient refers to any ingredient other than the active ingredient.
  • excipient will depend, to a large extent, on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form.
  • pharmaceutically acceptable excipients include, but are not limited to, excipients, diluents, fillers, binders, chelating agents, disintegrants, solubilizers, stabilizers, colorants, flavoring agents, surfactants, emulsifiers, buffers, or encapsulating materials.
  • stable pharmaceutical composition refers to a pharmaceutical composition in which the active ingredient (e.g., an antibody) substantially maintains its physical stability and/or chemical stability and/or biological activity when stored therein.
  • active ingredient e.g., an antibody
  • Stability can be measured at a selected temperature and under other storage conditions for a selected period of time.
  • the active ingredient does not show a significant increase in aggregation, precipitation and/or denaturation after visual inspection of color and/or clarity, or as measured by UV light scattering, size exclusion chromatography (SEC) and differential scanning calorimetry (DSC), then the active ingredient is stable.
  • the active ingredient "retains its physical stability” in the pharmaceutical composition.
  • An active ingredient e.g., an antibody
  • Chemical stability can be assessed by detecting and quantifying chemically altered forms of antibodies.
  • Processes that change the chemical structure of an antibody include hydrolysis or truncation (which can be evaluated by methods such as size exclusion chromatography and SDS-PAGE), oxidation (which can be evaluated by methods such as peptide mapping in combination with mass spectrometry or MALDI/TOF/MS), deamidation (which can be evaluated by methods such as ion exchange chromatography, capillary isoelectric focusing electrophoresis, peptide mapping, isoaspartate measurement), and isomerization (which can be evaluated by measuring isoaspartate content, peptide mapping, etc.).
  • hydrolysis or truncation which can be evaluated by methods such as size exclusion chromatography and SDS-PAGE
  • oxidation which can be evaluated by methods such as peptide mapping in combination with mass spectrometry or MALDI/TOF/MS
  • deamidation which can be evaluated by methods such as ion exchange chromatography, capillary isoelectric focusing electrophoresis, peptid
  • An active ingredient e.g., an antibody "retains its biological activity" in a pharmaceutical composition for a given time if its biological activity for a given time is within a predetermined range of the biological activity exhibited when the pharmaceutical composition is prepared, which can be determined by an antigen binding assay.
  • High molecular weight impurities or “aggregates” are a general term for impurities with a molecular weight greater than that of the target active ingredient (eg, antibody).
  • antibody refers to an antigen binding protein having at least one antigen binding domain.
  • the antibody or fragment thereof of the present disclosure may be a whole antibody or any fragment thereof, including a monoclonal antibody or fragment thereof and an antibody variant or fragment thereof.
  • Examples of antibodies or antigen binding fragments thereof of the present disclosure include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)' 2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv) and other antibody fragments known in the art.
  • “antibodies or antigen binding fragments thereof” of the present disclosure include whole antibodies and any antigen binding fragments or single chains thereof.
  • Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH).
  • the heavy chain constant region consists of three domains, namely CH1, CH2 and CH3.
  • Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL).
  • the light chain constant region is composed of a domain CL.
  • the VH and VL regions can also be divided into hypervariable regions, i.e., complementary determining regions (CDRs), and framework regions (FRs) with relatively conservative sequences.
  • Each VH and VL is composed of three CDRs and four FRs, respectively, from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the variable region of an antibody comprises a binding domain that interacts with an antigen.
  • the constant region of an antibody can mediate the binding of an immunoglobulin to a host tissue or factor, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.
  • a special "whole antibody" such as a nanobody, has only a heavy (H) chain and no light (L) chain.
  • the "antigen-binding fragment” of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen. It has been demonstrated that the antigen-binding function of an antibody can be implemented by a fragment of the entire antibody. Examples encompassed in the "antigen-binding fragment” of an antibody include: (i) Fab fragment: a monovalent fragment consisting of VL, VH, CL, and CH1 domains; (ii) F(ab') 2 fragment, a bivalent fragment comprising two Fab fragments connected by a disulfide bridge in the hinge region; (iii) Fd fragment consisting of VH and CH1 domains; (iv) Fv fragment consisting of the VL and VH domains of a single antibody arm; (v) dAb fragment consisting of a VH domain (see Ward et al., Nature.
  • VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH are paired to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)).
  • scFv single-chain Fv
  • antigen-binding fragment single-chain antibodies are also encompassed in the term antigen-binding fragment.
  • recombinant polypeptides, fusion proteins and immunoconjugates comprising the antigen-binding fragment are also encompassed in the term antigen-binding fragment.
  • a “chimeric antibody” is an antibody having at least a portion of a heavy chain variable region and at least a portion of a light chain variable region derived from one species; and at least a portion of a constant region derived from another species.
  • a chimeric antibody may comprise a murine variable region and a human constant region.
  • Humanized antibodies are antibodies that contain complementary determining regions (CDRs) derived from non-human antibodies, and framework regions and constant regions derived from human antibodies.
  • CDRs complementary determining regions
  • anti-TIM-3 antibodies and anti-PD-1 antibodies may contain CDRs derived from one or more murine antibodies, and human framework regions and human constant regions.
  • Additional anti-TIM-3 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein may be produced using any human framework sequence, and are also included in the present disclosure.
  • Additional anti-PD-1 antibodies or variants thereof comprising the HCDRs and LCDRs provided herein may be produced using any human framework sequence, and are also included in the present disclosure.
  • identity is also known as consistency.
  • the "percent identity (%)" of an amino acid sequence refers to the percentage of amino acid residues in the compared sequence that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after aligning the compared sequence with the specific amino acid sequence shown in this article and introducing gaps if necessary to achieve the maximum sequence identity percentage, and not considering any conservative substitutions as part of the sequence identity.
  • the alignment of amino acid sequences for identity can be performed in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for aligning sequences, including Any algorithms needed to achieve maximal alignment over the full length of the compared sequences are included.
  • fixed dose ratio refers to two or more different antibodies or antigen-binding fragments thereof in a single pharmaceutical composition that are present in a specific (fixed) ratio relative to each other in the pharmaceutical composition, the ratio being the fixed dose ratio.
  • the fixed dose ratio is based on the mass (e.g., mg) of the antibody or antigen-binding fragment thereof.
  • the fixed dose ratio is based on the concentration (e.g., mg/mL) of the antibody or antigen-binding fragment thereof.
  • multiples/fractions refer to multiples or fractions of a parameter/value.
  • multiples of 200 mg include 400 mg (2 times), 600 mg (3 times), 800 mg (4 times), and 1000 mg (5 times); fractions of 200 mg include 20 mg (1/10), 25 mg (1/8), 40 mg (1/5), 50 mg (1/4), and 100 mg (1/2).
  • treatment generally refers to an operation to obtain a desired pharmacological and/or physiological effect.
  • the effect may be preventive, in terms of completely or partially preventing a disease or its symptoms; and/or therapeutic, in terms of partially or completely stabilizing or curing a disease and/or side effects produced by the disease.
  • treatment encompasses any treatment of a patient's disease, including but not limited to preventing the occurrence or recurrence of a disease, alleviating symptoms of a disease, reducing any direct or indirect pathological consequences of a disease, preventing the metastasis of a disease, slowing the progression of a disease, improving or alleviating the state of a disease, extending the frequency and duration of symptom-free periods, and resolving or improving the prognosis of a disease.
  • “Therapeutically effective amount” or “therapeutically effective dose” refers to any amount of a drug that protects a subject from the onset of disease or promotes regression of disease, which can be demonstrated by a reduction in the severity of disease symptoms, an increase in the frequency and duration of disease symptom-free periods, or the prevention of impairment or disability caused by disease affliction.
  • the ability of a therapeutic agent to promote disease regression can be evaluated using a variety of methods known to skilled practitioners, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by measuring the activity of the agent in in vitro assays.
  • administering refers to the physical introduction of a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those skilled in the art.
  • the terms “subject”, “patient” or “subject” are used interchangeably.
  • “Subject”, “patient” or “subject” includes any person or non-human animal.
  • the term “non-human animal” includes, but is not limited to, vertebrates such as non-human primates, sheep, dogs, and rodents (such as mice, rats and guinea pigs).
  • the subject, patient or subject is a mammal.
  • the subject, patient or subject is a mouse.
  • the subject, patient or subject is a human.
  • a pharmaceutical composition refers to one pharmaceutical composition or more than one pharmaceutical composition.
  • “about” means within the acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” may mean within 1 or more than 1 standard deviation as practiced in the art. Alternatively, “about” may mean a range of up to ⁇ 5%, such as fluctuations within ⁇ 2%, within ⁇ 1%, or within ⁇ 0.5% of a given specific numerical range. When specific values or parameters are given herein or in the claims, they are modified by “about” by default unless otherwise indicated.
  • the words “comprise”, “include” and “contain” will be understood to mean including the stated step or element or group of steps or elements, but not excluding any other step or element or group of steps or elements.
  • Consisting of means including and limited to what follows the phrase “consisting of”. Thus, the phrase “consisting of” means that the listed elements are required or necessary, and no other elements may be present.
  • Consisting essentially of means including any element listed after the phrase, and is limited to other elements that do not interfere with or contribute to the activity or action of the listed elements. Thus, the phrase “consisting essentially of” means that the listed elements are required or necessary, but other elements are optional and may be present or absent depending on whether they affect the activity or action of the listed elements.
  • any concentration range, percentage range, ratio range or integer range should be understood to include the value of any integer within the range, and where appropriate, include fractions thereof (such as tenths and hundredths of integers), unless otherwise specified.
  • the present disclosure provides a pharmaceutical composition, wherein the pharmaceutical composition comprises an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof.
  • the second antibody or an antigen-binding fragment thereof is an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • a pharmaceutical composition when two or more antibodies or antigen-binding fragments thereof are included in a "pharmaceutical composition", the two or more antibodies or antigen-binding fragments thereof are formulated together and stored in a single vial or container (e.g., injection device) as a combined product, rather than being formulated and stored separately and then mixed before administration or administered separately.
  • the purpose of a pharmaceutical composition is to make the active ingredients (e.g., two or more antibodies or antigen-binding fragments thereof) suitable for production and/or administration to a patient, and to maintain biological activity and/or stability during storage and subsequent use.
  • the pharmaceutical composition of the present disclosure is an injection.
  • the injection includes but is not limited to a non-lyophilized water-soluble preparation or a water-soluble preparation reconstituted from a lyophilized preparation.
  • the anti-PD-1 antibody or its antigen-binding fragment and the anti-TIM-3 antibody or its antigen-binding fragment are present in the pharmaceutical composition at a fixed dose ratio.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1: 1-30, 1: 1-20, 1: 1-18, 1: 1-15, 1: 1-12, 1: 1-10, 1: 1-9, 1: 1-7.5, 1: 1-6, 1: 1-5, 1: 1-4.5, 1: 1-3, 1: 1-2 or 1: 1-1.5.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1: 1-6. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 30:1, 20:1, 18:1, 15:1, 12:1, 10:1, 9:1, 7.5:1, 6:1, 5:1, 4.5:1, 3:1, 2:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:3, 1:4.5, 1:5, 1:6, 1:7.5, 1:9, 1:10, 1:12, 1:15, 1:18, 1:20 or 1:30.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1:2, 1:3, 1:6 or 1:7.5. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1:2, 1:3, or 1:6. In some embodiments, the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical composition is 1:6.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, such as 100 mg, or 200 mg, or multiples/fractions thereof. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or 200 mg. In some embodiments, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg.
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions thereof, such as 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 2000 mg, or 2400 mg, or multiples/fractions thereof.
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or multiples/fractions thereof.
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 900 mg or 1200 mg.
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition comprises 100-200 mg, or multiples/fractions of any numerical value within the range thereof, of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any numerical value within the range thereof, of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 100 mg, or 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 2000 mg, or 2400 mg, or multiples/fractions thereof of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 200 mg, or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 300 mg, 600 mg, 900 mg, 1200 mg, 1500 mg, or 1800 mg, or multiples/fractions thereof of an anti-TIM-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 200 mg or multiples/fractions of anti-PD-1 antibodies or antigen-binding fragments thereof, and 600 mg, 1200 mg, or 1500 mg, or multiples/fractions of anti-TIM-3 antibodies or antigen-binding fragments thereof.
  • the pharmaceutical composition comprises 200 mg or multiples/fractions of anti-PD-1 antibodies or antigen-binding fragments thereof, and 600 mg, or 1200 mg, or multiples/fractions of anti-TIM-3 antibodies or antigen-binding fragments thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibodies or antigen-binding fragments thereof, and 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions of anti-TIM-3 antibodies or antigen-binding fragments thereof.
  • the pharmaceutical composition comprises 100 mg or multiples/fractions of anti-PD-1 antibodies or antigen-binding fragments thereof, and 300 mg or 600 mg, or multiples/fractions of anti-TIM-3 antibodies or antigen-binding fragments thereof. In some embodiments, the pharmaceutical composition comprises 100 mg or 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 600 mg or 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof. In some embodiments, the pharmaceutical composition comprises 100 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 600 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the fixed dose ratio is the concentration ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical composition.
  • the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment includes but is not limited to: 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8 mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15 mg/mL, 20 mg/mL, 21 mg/mL, 22 mg/mL, 23 mg/mL, 24 mg/mL, 25 mg/mL, 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL, 70 mg/mL, or 80 mg/mL, or a range formed by any two of the above values.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 8 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 10 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 15 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is 20 mg/mL.
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment includes but is not limited to: 3 mg/mL, 6 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL, 25 mg/mL, 30 mg/mL, 35 mg/mL, 40 mg/mL, 45 mg/mL, 50 mg/mL, 55 mg/mL, 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, 90 mg/mL, 100 mg/mL, 120 mg/mL, 150 mg/mL, or 180 mg/mL, or a range formed by any two of the above values.
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 24 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 45 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 48 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 60 mg/mL. In some embodiments, the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 90 mg/mL.
  • the pharmaceutical composition comprises 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL of an anti-PD-1 antibody or an antigen-binding fragment thereof, and 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL, 8 mg/mL, 9 mg/mL, 10 mg/mL, 11 mg/mL, 12 mg/mL, 13 mg/mL, 14 mg/mL, 15 mg/mL, 20 mg/mL, 21 mg/mL, 22 mg/mL, 23 mg/mL, 24 mg/mL, 25 mg/mL, 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL, 70 mg/mL, or 80 mg/mL.
  • an anti-PD-1 antibody or an antigen-binding fragment thereof, and 3 mg/mL, 6 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL, 25 mg/mL, 30 mg/mL, 35 mg/mL, 40 mg/mL, 45 mg/mL, 50 mg/mL, 55 mg/mL, 60 mg/mL, 65 mg/mL, 70 mg/mL, 75 mg/mL, 80 mg/mL, 90 mg/mL, 100 mg/mL, 120 mg/mL, 150 mg/mL, or 180 mg/mL of an anti-TIM-3 antibody, or an antigen-binding fragment thereof.
  • the pharmaceutical composition comprises 5 mg/mL, 8 mg/mL, 10 mg/mL or 15 mg/mL of anti-PD-1 antibody or its antigen-binding fragment, and 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL, 60 mg/mL or 90 mg/mL of anti-TIM-3 antibody or its antigen-binding fragment.
  • the pharmaceutical composition comprises 5 mg/mL or 10 mg/mL of anti-PD-1 antibody or its antigen-binding fragment, and 15 mg/mL, 30 mg/mL or 60 mg/mL of anti-TIM-3 antibody or its antigen-binding fragment.
  • the pharmaceutical composition comprises 5 mg/mL of anti-PD-1 antibody or its antigen-binding fragment, and 30 mg/mL of anti-TIM-3 antibody or its antigen-binding fragment. In some embodiments, the pharmaceutical composition comprises 5 mg/mL of anti-PD-1 antibody or its antigen-binding fragment, and 15 mg/mL of anti-TIM-3 antibody or its antigen-binding fragment.
  • the pharmaceutical composition of the present disclosure may also contain one or more pharmaceutically acceptable excipients, such as buffers, stabilizers, diluents, chelating agents, and surfactants.
  • pharmaceutically acceptable excipients such as buffers, stabilizers, diluents, chelating agents, and surfactants.
  • the pharmaceutical composition of the present disclosure further comprises a buffer.
  • the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer and/or a citrate buffer.
  • the buffer comprises a histidine buffer and/or an acetate buffer.
  • the buffer comprises a histidine buffer.
  • the histidine buffer can be histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, histidine-acetate buffer or histidine-phosphate buffer. In some embodiments, the histidine buffer can be histidine-acetate buffer. In some embodiments, the acetate buffer can be sodium acetate buffer, potassium acetate buffer or ammonium acetate buffer. In some embodiments, the phosphate buffer can be sodium phosphate buffer or potassium phosphate buffer. In some embodiments, the citrate buffer can be sodium citrate buffer, potassium citrate buffer or calcium citrate buffer.
  • the concentration of the buffer is 1-100mM, 2-80mM, 5-60mM, 10-40mM, or 10-20mM. In some embodiments, the concentration of the buffer includes but is not limited to: 5mM, 10mM, 11mM, 12mM, 13mM, 14mM, 15mM, 16mM, 17mM, 18mM, 19mM, 20mM, 21mM, 22mM, 23mM, 24mM, 25mM, 26mM, 27mM, 28mM, 29mM, 30mM, 32mM, 34mM, 36mM, 38mM, 40mM, 50mm, or 60mM, or the range formed by any two of the above values. In some embodiments, the concentration of the buffer is 10mM. In some embodiments, the concentration of the buffer is 20mM. In some embodiments, the buffer comprises a histidine buffer. In some embodiments, the buffer comprises a histidine-acetate buffer.
  • the pH of the buffer is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pH of the buffer includes but is not limited to: 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7, or a range formed by any two of the above values.
  • the pH of the buffer is 5.5.
  • the pH of the buffer is 5.8.
  • the pH of the buffer is 6.
  • the pH of the buffer is 6.2.
  • the pH of the buffer is 6.5.
  • the pharmaceutical composition of the present disclosure also includes a stabilizer.
  • the stabilizer includes a sugar alcohol (e.g., mannitol, sorbitol), a disaccharide (e.g., trehalose, sucrose, maltose, lactose), a monosaccharide (e.g., dextrose (D-glucose)), an amino acid (e.g., lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof), and/or a salt (e.g., sodium chloride).
  • a sugar alcohol e.g., mannitol, sorbitol
  • a disaccharide e.g., trehalose, sucrose, maltose, lactose
  • a monosaccharide e.g., dextrose (D-glucose)
  • an amino acid e.g., lysine, glycine, proline,
  • the stabilizer includes mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof and/or sodium chloride.
  • the stabilizer includes a sugar alcohol (e.g., sorbitol) or a disaccharide (e.g., sucrose or trehalose).
  • the stabilizer includes sucrose.
  • the concentration of the stabilizer is 1-400 mg/mL, 10-300 mg/mL, 20-200 mg/mL, 40-200 mg/mL, 40-180 mg/mL, 60-180 mg/mL, or 70-170 mg/mL.
  • the concentration of the stabilizer includes but is not limited to: 10 mg/mL, 20 mg/mL, 24 mg/mL, 30 mg/mL, 40 mg/mL, 45 mg/mL, 50 mg/mL, 54 mg/mL, 60 mg/mL, 65 mg/mL, 70 mg/mL, 80 mg/mL, 85 mg/mL, 89 mg/mL, 90 mg/mL, 100 mg/mL, 110 mg/mL, 113 mg/mL, 120 mg/mL, 130 mg/mL, 140 mg/mL, 150 mg/mL, 154 160 mg/mL, 164 mg/mL, 170 mg/mL, 178 mg/mL, 180 mg/mL, 190 mg/mL, 200 mg/mL, 202 mg/mL, 210 mg/mL, 220 mg/mL, 230 mg/mL, 240 mg/mL, 243 mg/mL, 250 mg/mL, 260 mg/mL,
  • the concentration of the stabilizer includes but is not limited to: 10.3 mg/mL, 13.7 mg/mL, 17.1 mg/mL, 20.5 mg/mL, 27.4 mg/mL, 30.8 mg/mL, 34.2 mg/mL, 34.5 mg/mL, 37.7 mg/mL, 41.1 mg/mL, 44.5 mg/mL, 47.9 mg/mL, 51.3 mg/mL, 54.8 mg/mL, 58.2 mg/mL, 61.6 mg/mL, 68.5 mg/mL, 71.9 mg/mL, 75.3 mg/mL, 78.7 mg/mL , 82.2mg/mL, 85.6mg/mL, 92.4mg/mL, 95.8mg/mL, 99.3mg/mL, 102.7mg/mL, 106.1mg/mL, 108.1mg/mL, 109.5mg/mL, 116.4mg/mL, 119.8m g
  • the concentration of the stabilizer is 80-164.3 mg/mL. In some embodiments, the concentration of the stabilizer is 80 mg/mL. In some embodiments, the concentration of the stabilizer is 85 mg/mL. In some embodiments, the concentration of the stabilizer is 85.6 mg/mL. In some embodiments, the concentration of the stabilizer is 100 mg/mL. In some embodiments, the concentration of the stabilizer is 164 mg/mL. In some embodiments, the concentration of the stabilizer is 164.3 mg/mL. In some embodiments, the stabilizer comprises sucrose.
  • the concentration of the stabilizer is 30mM-960mM, 60mM-720mM, 120mM-480mM, 240mM-480mM, 210mM-270mM, 230mM-250mM, 450mM-510mM, or 470mM-490mM. In some embodiments, the concentration of the stabilizer is 100-800mM, 200-700mM, 300-600mM, 400-500mM, or 470-490mM.
  • the concentration of the stabilizer includes but is not limited to: 30mM, 60mM, 90mM, 100mM, 120mM, 150mM, 160mM, 175mM, 180mM, 200mM, 210mM, 230mM, 234mM, 240mM, 250mM, 270mM, 300mM, 330mM, 360mM, 390mM, 400mM, 420mM, 450mM, In some embodiments, the concentration of the stabilizer is 200-500mM. In some embodiments, the concentration of the stabilizer is 230-480mM. In some embodiments, the concentration of the stabilizer is 400-500mM. In some embodiments, the concentration of the stabilizer is 230mM.
  • the concentration of the stabilizer is 234mM. In some embodiments, the concentration of the stabilizer is 240 mM. In some embodiments, the concentration of the stabilizer is 300 mM. In some embodiments, the concentration of the stabilizer is 480 mM. In some embodiments, the stabilizer comprises sucrose.
  • the pharmaceutical composition of the present disclosure also includes a surfactant.
  • the surfactant is a nonionic surfactant.
  • the surfactant includes polysorbate (e.g., polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, polysorbate 81, polysorbate 85), poloxamer (e.g., poloxamer 181, poloxamer 188, poloxamer 407) and/or polyethylene glycol etc.
  • the surfactant includes polysorbate (e.g., polysorbate 80 or polysorbate 20).
  • the surfactant includes polysorbate 80.
  • the concentration of the surfactant is 0.01-3 mg/mL, 0.04-2 mg/mL, 0.08-1.6 mg/mL, 0.1-1.2 mg/mL, 0.1-1 mg/mL, 0.2-0.8 mg/mL, or 0.4-0.8 mg/mL.
  • the concentration of the surfactant includes but is not limited to: 0.01mg/mL, 0.04mg/mL, 0.06mg/mL, 0.08mg/mL, 0.1mg/mL, 0.15mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL, 0.5mg/mL, 0.6mg/mL, 0.7mg/mL, 0.8mg/mL, 0.9mg/mL, 1mg/mL, 1.1mg/mL, 1.2mg/mL, 1.3mg/mL, 1.4mg/mL, 1.5mg/mL, 1.6mg/mL or 2mg/mL or the range formed by any two of the above values.
  • the concentration of the surfactant is 0.2mg/mL. In some embodiments, the concentration of the surfactant is 0.4mg/mL. In some embodiments, the concentration of the surfactant is 0.5mg/mL. In some embodiments, the concentration of the surfactant is 0.6mg/mL. In some embodiments, the concentration of the surfactant is 0.8 mg/mL.In some embodiments, the surfactant comprises polysorbate 80.
  • the pH of the pharmaceutical composition of the present disclosure is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pH of the pharmaceutical composition of the present disclosure includes but is not limited to: 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, or 7, or the range formed by any two of the above values.
  • the pH of the pharmaceutical composition is 5.5.
  • the pH of the pharmaceutical composition of the present disclosure is 5.8.
  • the pH of the pharmaceutical composition of the present disclosure is 6.
  • the pH of the pharmaceutical composition of the present disclosure is 6.2.
  • the pH of the pharmaceutical composition of the present disclosure is 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) a stabilizer, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6).
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) a stabilizer, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5).
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or its antigen-binding fragment and an anti-TIM-3 antibody or its antigen-binding fragment, (b) a buffer, (c) a stabilizer, and (d) a surfactant; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5). The fixed dose ratio is 1:3, 1:6 or 1:7.5.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) 1-400 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.01-3 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20 ); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) 1-400 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.01-3 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., a histidine buffer), (c) 1-400 mg/mL stabilizer (e.g., sucrose), and (d) 0.01-3 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., a histidine buffer
  • stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, The concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 2-80 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 10-300 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) a 0.04-2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20 ); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • a 2-80 mM buffer e.g.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., acetate buffer or histidine buffer), (c) 10-300 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.04-2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • 2-80 mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., histidine buffer), (c) 10-300 mg/mL stabilizer (e.g., sucrose), and (d) 0.04-2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 2-80 mM buffer e.g., histidine buffer
  • 10-300 mg/mL stabilizer e.g., sucrose
  • 0.04-2 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 5-60 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 20-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.08-1.6 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20).
  • a 5-60 mM buffer e.g., an acetate buffer or a histidine buffer
  • a 20-200 mg/mL stabilizer e.g., sorbitol or sucrose
  • 0.08-1.6 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., acetate buffer or histidine buffer), (c) 20-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.08-1.6 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • 5-60 mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., histidine buffer), (c) 20-200 mg/mL stabilizer (e.g., sucrose), and (d) 0.08-1.6 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 5-60 mM buffer e.g., histidine buffer
  • 20-200 mg/mL stabilizer e.g., sucrose
  • 0.08-1.6 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 10-40 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 40-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) a 0.1-1.2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20).
  • a 10-40 mM buffer e.g., an acetate buffer or a histidine buffer
  • a 40-200 mg/mL stabilizer e.g., sorbitol or sucrose
  • a 0.1-1.2 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or its antigen-binding fragment and an anti-TIM-3 antibody or its antigen-binding fragment, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) 40-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.1-1.2 mg/mL surfactant.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., 0.1-1.2 mg/mL surfactant.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 10-40 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 40-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) a 0.1-1 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20 ); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • a 10-40 mM buffer e.g
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) 40-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.1-1 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., histidine buffer), (c) 40-180 mg/mL stabilizer (e.g., sucrose), and (d) 0.1-1 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • 40-180 mg/mL stabilizer e.g., sucrose
  • 0.1-1 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 60-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) a 0.2-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20).
  • a 10-20 mM buffer e.g., an acetate buffer or a histidine buffer
  • a 60-180 mg/mL stabilizer e.g., sorbitol or sucrose
  • a 0.2-0.8 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., acetate buffer or histidine buffer), (c) 60-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.2-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer), (c) 60-180 mg/mL stabilizer (e.g., sucrose), and (d) 0.2-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or Its multiple/fraction
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or a multiple/fraction of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or a multiple/fraction thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or a multiple/fraction thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or a multiple/fraction thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or a multiple/fraction thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or a multiple/fraction thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or a multiple/fraction thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 10-20 mM buffer (e.g., an acetate buffer or a histidine buffer), (c) a 70-170 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) a 0.4-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20).
  • a 10-20 mM buffer e.g., an acetate buffer or a histidine buffer
  • a 70-170 mg/mL stabilizer e.g., sorbitol or sucrose
  • a 0.4-0.8 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20.
  • the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5 (e.g., 1:1-7.5 or 1:1-6), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., acetate buffer or histidine buffer), (c) 70-170 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.4-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1.5, 1:3, 1:4.5, 1:6, 1:7.5 or 1:9 (e.g., 1:2, 1:3, 1:6 or 1:7.5), and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., a histidine buffer), (c) 70-170 mg/mL stabilizer (e.g., sucrose), and (d) 0.4-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., a histidine buffer
  • 70-170 mg/mL stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100-200 mg, or multiples/fractions of any value within the range thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a 10-40 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer agent, histidine-HCl buffer, or histidine-acetate buffer), (c) 40-200 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.1-1.2 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 40-180 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 1 64.3 mg/mL sucrose), and (d) 0.1-1 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 16
  • the invention relates to an embodiment of the present invention wherein the fixed dose ratio of the anti-PD-1 antibody or antigen-binding fragment thereof to the anti-TIM-3 antibody or antigen-binding fragment thereof is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 60-180 mg/mL sucrose e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL.
  • 0.2-0.8mg/mL polysorbate 80 e.g., 0.2mg/mL, 0.4mg/mL, 0.5mg/mL, 0.6mg/mL or 0.8mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20mg/mL, 5-20mg/mL, 5-15mg/mL, or 5-10mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90mg/mL, 15-90mg/mL, 15-60mg/mL, or 30-60mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or its multiple/fraction
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or its multiple/fraction.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or its multiple/fraction
  • the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or its multiple/fraction.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or its multiple/fraction, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or its multiple/fraction. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 70-170 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 70-170 mg/mL sucrose e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL.
  • 0.4-0.8 mg/mL polysorbate 80 e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 70-170 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL , 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 80-164.3 mg/mL sucrose e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL.
  • 0.4-0.8 mg/mL polysorbate 80 e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydro
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 200-500 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM).
  • 10-20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 200-500 mM sucrose e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM.
  • 0.4-0.8 mg/mL polysorbate 80 e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 10-20 mM histidine buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the The pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 20 mM histidine buffer e.g., 20 mM histidine-acetate buffer
  • 230-480 mM sucrose e.g., 230 mM, 234 mM
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-acetate buffer), (c) 400-500 mM sucrose (e.g., 480 mM sucrose), and (d) 0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:6, and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600-1500 mg, or 600-1200 mg, or multiples/fractions of any value within the range thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 200 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg, 1200 mg, or 1500 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg, 600 mg, 750 mg, or 900 mg, or multiples/fractions thereof.
  • the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg or multiples/fractions thereof, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 300 mg or 600 mg, or multiples/fractions thereof. In the specific embodiment, the mass of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg, and the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 600 mg.
  • the pharmaceutical composition of the present disclosure comprises: (a) 200 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg, or 1200 mg, or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mM g/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH
  • the pharmaceutical composition of the present disclosure comprises: (a) 200 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg, or 1200 mg, or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 70 -170 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.5 to 6.5
  • the pharmaceutical composition of the present invention comprises: (a) 200 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg, or 1200 mg, or multiples/fractions thereof of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10 mM or 20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL or 164.3 mg/mL sucrose, and (d) 0.4 mg/mL or 0.8 mg/mL polysorbate 80; wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 10 mM or 20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the pharmaceutical composition of the present disclosure comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60- 180 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.5 to 6.5
  • the pharmaceutical composition of the present disclosure comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 70-170 mM g/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3
  • the invention relates to a pharmaceutical composition comprising: (a) 0.5 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH
  • the pharmaceutical composition of the present invention comprises: (a) 90-110 mg or multiples/fractions thereof of an anti-PD-1 antibody or an antigen-binding fragment thereof and 540-660 mg or multiples/fractions thereof of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 15-25 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 150-180 mg/mL sucrose (e.g., 164.3 mg/mL sucrose), and (d) 0.7-0.9 mg/mL polysorbate 80 (e.g., 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.3 to 6.3, 5.5 to 6.5, or 5.8 to 6.5.
  • mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or
  • the pharmaceutical composition of the present invention comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present invention comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3 mg/mL sucrose (e.g., 80 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.8 mg/mL polysorbate 80; wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-a
  • the pharmaceutical composition of the present invention comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.8 mg/mL polysorbate 80; wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • the pharmaceutical composition of the present invention comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10 mM or 20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL or 164.3 mg/mL sucrose, and (d) 0.4 mg/mL or 0.8 mg/mL polysorbate 80; wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 10 mM or 20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • the pharmaceutical composition of the present invention comprises: (a) 100 mg or multiples/fractions of an anti-PD-1 antibody or an antigen-binding fragment thereof and 600 mg or multiples/fractions of an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10 mM or 20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 234 mM or 480 mM sucrose, and (d) 0.4 mg/mL or 0.8 mg/mL polysorbate 80; wherein the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 10 mM or 20 mM histidine buffer e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • the pharmaceutical composition of the present disclosure comprises: (a) 90-110 mg or multiples/fractions of anti-PD-1 antibody or antigen-binding fragment thereof and 540-660 mg or multiples/fractions of anti-TIM-3 antibody or antigen-binding fragment thereof, (b) 15-25 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 450-510 mM sucrose (e.g., 480 mM sucrose), and (d) 0.7-0.9 mg/mL polysorbate 80 (e.g., 0.8 mg/mL polysorbate 80); wherein the pH of the pharmaceutical composition is 5.3 to 6.3, 5.5 to 6.5, or 5.8 to 6.5.
  • histidine buffer e.g. 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • the anti-PD-1 antibody or its anti- The concentration of the original binding fragment is 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL
  • the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 15-60 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5-10 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30-60 mg/mL. In the specific embodiment, the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 5 mg/mL, and the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 30 mg/mL.
  • the pharmaceutical composition of the present disclosure comprises: (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) a stabilizer, and (d) a surfactant.
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 1-200 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., acetate buffer or histidine buffer), (c) 1-400 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.01-3 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-80 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 3-180 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., acetate buffer or histidine buffer), (c) 10-300 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.04-2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • 2-80 mM buffer e.g., acetate buffer or histidine buffer
  • 10-300 mg/mL stabilizer e.g., sorbitol or sucrose
  • 0.04-2 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7,
  • the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 6-120 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 5-60 mM buffer (e.g., acetate buffer or histidine buffer), (c) 20-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.08-1.6 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • 5-60 mM buffer e.g., acetate buffer or histidine buffer
  • 20-200 mg/mL stabilizer e.g., sorbitol or sucrose
  • 0.08-1.6 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7,
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 10-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) 40-200 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.1-1.2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • 40-200 mg/mL stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., acetate buffer or histidine buffer), (c) 40-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.1-1 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • 40-180 mg/mL stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., acetate buffer or histidine buffer), (c) 60-180 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.2-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL, or 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., acetate buffer or histidine buffer), (c) 70-170 mg/mL stabilizer (e.g., sorbitol or sucrose), and (d) 0.4-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., acetate buffer or histidine buffer
  • 70-170 mg/mL stabilizer e.g., sorbitol or sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5 to 7, 5.5 to
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-100 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 1-200 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 1-100 mM buffer (e.g., histidine buffer), (c) 1-400 mg/mL stabilizer (e.g., sucrose), and (d) 0.01-3 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pharmaceutical composition of the present disclosure comprises: (a) 1-80 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 3-180 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 2-80 mM buffer (e.g., histidine buffer), (c) 10-300 mg/mL stabilizer (e.g., sucrose), and (d) 0.04-2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 2-80 mM buffer e.g., histidine buffer
  • 10-300 mg/mL stabilizer e.g., sucrose
  • 0.04-2 mg/mL surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 2-60 mg/mL anti-PD-1 antibody or its antigen-binding fragment and 6-120 mg/mL anti-TIM-3 antibody or its antigen-binding fragment, (b) 5-60 mM buffer (e.g., histidine buffer), (c) 20-200 mg/mL A stabilizer (e.g., sucrose), and (d) 0.08-1.6 mg/mL of a surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 5-60 mM buffer e.g., histidine buffer
  • 20-200 mg/mL A stabilizer e.g., sucrose
  • a surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 10-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., histidine buffer), (c) 40-200 mg/mL stabilizer (e.g., sucrose), and (d) 0.1-1.2 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • 40-200 mg/mL stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-40 mM buffer (e.g., histidine buffer), (c) 40-180 mg/mL stabilizer (e.g., sucrose), and (d) 0.1-1 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • 40-180 mg/mL stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer), (c) 60-180 mg/mL stabilizer (e.g., sucrose), and (d) 0.2-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL, or 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM buffer (e.g., histidine buffer), (c) 70-170 mg/mL stabilizer (e.g., sucrose), and (d) 0.4-0.8 mg/mL surfactant (e.g., polysorbate 80 or polysorbate 20); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • mM buffer e.g., histidine buffer
  • 70-170 mg/mL stabilizer e.g., sucrose
  • surfactant e.g., polysorbate 80 or polysorbate 20
  • the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL, 10 mg/mL, 15 mg/mL, 20 mg/mL or 30 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 10-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL, 60 mg/mL or 90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-40 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 40-200 mg/mL sucrose (e.g., 80 mg
  • the pharmaceutical composition of the present disclosure comprises: (a) 3-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL, 10 mg/mL, 15 mg/mL or 20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 15-90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL, 60 mg/mL or 90 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-40 mM histidine buffer (e.g.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL, 10 mg/mL, 15 mg/mL or 20 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL, 85 mg/mL, 85.6
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer,
  • the pharmaceutical composition comprises: (a) 5-10 ⁇ g/mL sodium bicarbonate buffer (e.g., 5-10 ⁇ g/mL sodium bicarbonate buffer, 5-10 ⁇ g/mL sodium bicarbonate buffer, 5-10 ⁇ g/mL sodium bi
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-15 mg/mL, or 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL, 10 mg/mL or 15 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 70-170mg/mL sucrose (e.g., 80mg/mL, 85mg/mL, 85.6mg
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 15-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 15 mg/mL, 24 mg/mL, 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-
  • the pharmaceutical composition comprises: (a) a prepolymer of at least one alkylene glycol and/or a hydroxyl radical of at least one alkylene glycol; (b) a prepolymer of at least one alkylene glycol and/or a hydroxyl radical of at least at least
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 30-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer).
  • 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof
  • granules (c) 70-170 mg/mL sucrose (e.g., 80 mg/mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose) or 200-500 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); and the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • sucrose e.g. 80 mg/mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose
  • 200-500 mM sucrose e.g., 230 m
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 30-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride).
  • 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof
  • the pharmaceutical composition of the present disclosure comprises: (a) 5-10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL, 8 mg/mL or 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 30-60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 30 mg/mL, 45 mg/mL, 48 mg/mL or 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 10-20 mM histidine buffer (e.g., 10).
  • the pharmaceutical composition comprises: (a) 20 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5
  • the pharmaceutical composition of the present disclosure comprises: (a) 8 mg/mL anti-PD-1 antibody or antigen-binding fragment thereof and 24 mg/mL anti-TIM-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL
  • the pharmaceutical composition may further comprise (i) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); and (ii) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg
  • the pharmaceutical composition of the present disclosure comprises: (a) 8 mg/mL anti-PD-1 antibody or antigen-binding fragment thereof and 48 mg/mL anti-TIM-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL
  • the pharmaceutical composition may further comprise (i) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); and (ii) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg
  • the pharmaceutical composition of the present disclosure comprises: (a) 10 mg/mL anti-PD-1 antibody or antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL /mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to
  • the pharmaceutical composition of the present disclosure comprises: (a) 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL /mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 10 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 60 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL sucrose, and (d) 0.2 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 80 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pH of the pharmaceutical composition is
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 60-180 mg/mL sucrose (e.g., 80 mg/mL
  • the pharmaceutical composition may further comprise (i) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); and (ii) 0.2-0.8 mg/mL polysorbate 80 (e.g., 0.2 mg/mL, 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3 mg/mL sucrose (e.g., 80 mg/mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10-20 mM histidine buffer (e.g., 10 mM or 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.4-0.8 mg/mL polysorbate 80 (e.g., 0.4 mg/mL, 0.5 mg/mL, 0.6 mg/mL or 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5.
  • 10-20 mM histidine buffer e.g., 10 m
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80-164.3 mg/mL sucrose (e.g., 80 mg/mL, 85 mg/mL, 85.6 mg/mL, 100 mg/mL, 164 mg/mL or 164.3 mg/mL sucrose), and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydr
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 24-36 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 15-25 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 150-180 mg/mL sucrose (e.g., 164.3 mg/mL sucrose), and (d) 0.7-0.9 mg/mL polysorbate 80 (e.g., 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.3 to 6.3, 5.5 to 6.5, or 5.8 to 6.5 (e.g.,
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 164.3 mg/mL sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 164.3 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 230-480 mM sucrose (e.g., 230 mM, 234 mM, 400 mM, 450 mM or 480 mM sucrose), and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-
  • the pharmaceutical composition of the present disclosure comprises: (a) 4-6 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof (e.g., 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof) and 24-36 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof (e.g., 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof), (b) 15-25 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 450-510 mM sucrose (e.g., 480 mM sucrose), and (d) 0.7-0.9 mg/mL polysorbate 80 (e.g., 0.8 mg/mL polysorbate 80); the pH of the pharmaceutical composition is 5.3 to 6.3, 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 480 mM sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 480 mM sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pH of the pharmaceutical composition is
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 10 mM histidine buffer (e.g., 10 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 164.3 mg/mL sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 10 mM histidine buffer e.g., 10 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 164.3 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 80 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pH of the pharmaceutical composition is
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 30 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL sucrose, and (d) 0.4 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 80 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pH of the pharmaceutical composition is
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or antigen-binding fragment thereof and 15 mg/mL anti-TIM-3 antibody or antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL sucrose, and (d) 0.4 mg/mL polysorbate 80; the drug
  • the pH of the composition is 5.5 to 6.5, or 5.8 to 6.5 (eg, 5.5, 5.8, 6, 6.2, or 6.5).
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 80 mg/mL sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 80 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pH of the pharmaceutical composition is
  • the pharmaceutical composition of the present disclosure comprises: (a) 5 mg/mL anti-PD-1 antibody or an antigen-binding fragment thereof and 15 mg/mL anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) 20 mM histidine buffer (e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer), (c) 164.3 mg/mL sucrose, and (d) 0.8 mg/mL polysorbate 80; the pH of the pharmaceutical composition is 5.5 to 6.5, or 5.8 to 6.5 (e.g., 5.5, 5.8, 6, 6.2 or 6.5).
  • 20 mM histidine buffer e.g., 20 mM histidine-histidine hydrochloride buffer, histidine-hydrochloride buffer, or histidine-acetate buffer
  • 164.3 mg/mL sucrose e.g., 5.5, 5.8, 6, 6.2 or 6.5
  • the pharmaceutical compositions of the present disclosure can be stably stored at 2-8°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years.
  • the pharmaceutical compositions of the present disclosure can be stably stored at 25°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years.
  • the pharmaceutical compositions of the present disclosure can be stably stored at 40°C for at least about 1 week, at least about 2 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 6 months, at least about 9 months, at least about 1 year, or at least about 2 years.
  • the present disclosure also provides a lyophilized formulation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and a second antibody or an antigen-binding fragment thereof.
  • the second antibody or an antigen-binding fragment thereof is an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the present disclosure also provides a method for preparing the lyophilized preparation, which includes the step of freeze-drying the pharmaceutical composition of the present disclosure.
  • the freeze-drying is carried out according to methods well known in the art, including but not limited to the steps of pre-freezing, primary drying and secondary drying. It is understood by those skilled in the art that any method of removing water from the pharmaceutical composition of the present disclosure is applicable to the present disclosure. It is understood by those skilled in the art that in the pharmaceutical field, lyophilized preparations generally have a residual moisture content of about 0.1 to 5% (w/v) and are present as powders or physically stable cakes.
  • the present disclosure also provides a lyophilized preparation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, wherein the lyophilized preparation is prepared by the aforementioned method for preparing a lyophilized preparation.
  • the present disclosure also provides a lyophilized preparation comprising an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, which can form a pharmaceutical composition of the present disclosure after reconstitution.
  • the solution used for reconstitution includes but is not limited to water for injection, sodium chloride injection, Ringer's solution or glucose injection.
  • “reconstitution” and “redissolution” can be used interchangeably.
  • the anti-PD-1 antibody or antigen-binding fragment thereof described in the present disclosure comprises: a heavy chain CDR1 (HCDR1) of the amino acid sequence shown in SEQ ID NO:11, a HCDR2 of the amino acid sequence shown in SEQ ID NO:12, a HCDR3 of the amino acid sequence shown in SEQ ID NO:13, a light chain CDR1 (LCDR1) of the amino acid sequence shown in SEQ ID NO:14, a LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and a LCDR3 of the amino acid sequence shown in SEQ ID NO:16.
  • HCDR1 heavy chain CDR1
  • LCDR1 light chain CDR1
  • LCDR2 of the amino acid sequence shown in SEQ ID NO:15
  • LCDR3 of the amino acid sequence shown in SEQ ID NO:16.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region of the amino acid sequence shown in SEQ ID NO:17, and LCDR1, LCDR2 and LCDR3 in the light chain variable region of the amino acid sequence shown in SEQ ID NO:18.
  • the CDR sequences of the anti-PD-1 antibody or antigen-binding fragment thereof are shown in Table 1-1.
  • CDR complementarity determining region
  • a given antibody or region thereof e.g., variable region
  • CDR regions are shown in Table 1-1, however, when referring to antibodies defined by specific CDR sequences, the scope of the antibodies encompasses antibodies defined by CDR sequences defined by any numbering system (e.g., a combination of one or more of the definitions of AbM, Kabat, CCG, Chothia, IMGT, or Contact, etc., which are well known in the art). body.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region as shown in SEQ ID NO: 17.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region as shown in SEQ ID NO: 18.
  • the anti-PD-1 antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:17, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence as shown in SEQ ID NO: 18.
  • the amino acid sequence of the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 17, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 16, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17.
  • NO:17 has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:18.
  • the anti-PD-1 antibody or its antigen-binding fragment may further comprise a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region.
  • the constant region comprises a heavy chain constant region and a light chain constant region.
  • the heavy chain constant region is from a human immunoglobulin heavy chain, such as a heavy chain of IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulins, preferably a heavy chain of IgG1.
  • the light chain constant region is from a human immunoglobulin light chain, such as a ⁇ light chain or a ⁇ light chain of a human immunoglobulin.
  • the constant region may comprise any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids.
  • the constant region comprises a mutation that changes effector function.
  • any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 19.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain as set forth in SEQ ID NO: 19.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain as set forth in SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 19, and a light chain having an amino acid sequence as shown in SEQ ID NO: 20.
  • the heavy chain amino acid sequence of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 19, and the light chain amino acid sequence is as shown in SEQ ID NO: 20.
  • the terminal amino acid K of SEQ ID NO: 19 may be present or absent.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1 or 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2 or 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3 or 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4 or 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5 or 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6 or 26.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises: HCDR1, HCDR2 and HCDR3 in the heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 7, and LCDR1, LCDR2 and LCDR3 in the light chain variable region of the amino acid sequence shown in SEQ ID NO: 8.
  • the CDR sequences of the anti-TIM-3 antibody or antigen-binding fragment thereof are shown in Table 1-2.
  • CDR complementarity determining region
  • Tables 1-2 have shown CDR sequences (wherein the CDR regions shown in SEQ ID NOs: 1-6 are defined by the AbM numbering system), however, when referring to antibodies defined by specific CDR sequences disclosed herein, the scope of the antibodies also encompasses antibodies defined by CDR sequences converted to any other numbering system definition (e.g., one or more combinations of the definitions of Kabat, Chothia, CCG, IMGT or Contact, etc., which are well known in the art).
  • anti-TIM-3 antibodies or antigen-binding fragments thereof of the present disclosure are anti-TIM-3 antibodies or antigen-binding fragments thereof having the following sequence: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in ARRYYGYDAMDY (SEQ ID NO: 31), LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6.
  • the anti-TIM-3 antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:7 or 27.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 8 or 28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO: 7.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region as set forth in SEQ ID NO: 8.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:7 or 27, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:8 or 28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region of the amino acid sequence shown in SEQ ID NO:8.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO:27, and a light chain variable region of the amino acid sequence shown in SEQ ID NO:28.
  • the amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:8.
  • amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO:27, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO:28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 1, HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, HCDR3 comprises the amino acid sequence of SEQ ID NO: 3, LCDR1 comprises the amino acid sequence of SEQ ID NO: 4, LCDR2 comprises the amino acid sequence of SEQ ID NO: 5, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 6, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:8.
  • the anti-TIM-3 antibody or its antigen-binding fragment may also include a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region.
  • the constant region includes a heavy chain constant region and a light chain constant region.
  • the heavy chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG4 heavy chains.
  • the light chain constant region is from a human immunoglobulin light chain, such as a ⁇ light chain or a ⁇ light chain of a human immunoglobulin.
  • the constant region may include any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids.
  • the constant region includes a mutation that changes the effector function.
  • any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain as shown in SEQ ID NO: 9.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain as shown in SEQ ID NO: 10.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain of the amino acid sequence shown in SEQ ID NO: 9, and a light chain of the amino acid sequence shown in SEQ ID NO: 10. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain of the amino acid sequence shown in SEQ ID NO: 29, and a light chain of the amino acid sequence shown in SEQ ID NO: 30. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 9, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 10.
  • amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 29, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 30.
  • the terminal amino acid K of SEQ ID NO: 9 and 29 may be present or absent.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein is mAb 50B5 or an antigen-binding fragment thereof described in the patent application document with publication number CN112566936A, or a chimeric antibody or an antigen-binding fragment thereof of mAb 50B5, or a humanized antibody or an antigen-binding fragment thereof of mAb 50B5.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein is mAb 15B4 or an antigen-binding fragment thereof described in the patent application document with publication number CN112566936A, or a chimeric antibody or an antigen-binding fragment thereof of mAb 15B4, or a humanized antibody or an antigen-binding fragment thereof of mAb15B4.
  • the present disclosure relates to any method of preparing the pharmaceutical composition of the present disclosure.
  • the present disclosure provides a method for preparing a pharmaceutical composition of the present disclosure, comprising: mixing a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof with a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof in a desired ratio.
  • the pharmaceutical composition of the antibody or its antigen-binding fragment comprises the antibody or its antigen-binding fragment and a buffer, and optionally, further comprises a stabilizer and a surfactant.
  • the present disclosure provides a method for preparing a pharmaceutical composition of the present disclosure, comprising: contacting an anti-TIM-3 antibody or an antigen-binding fragment thereof with a buffer, a stabilizer and a surfactant, contacting an anti-PD-1 antibody or an antigen-binding fragment thereof with a buffer, a stabilizer and a surfactant, and mixing the two in a desired ratio.
  • the step of contacting the antibody or its antigen-binding fragment with a buffer, a stabilizer and a surfactant comprises replacing the antibody or its antigen-binding fragment into a buffer, and then adding a surfactant and a stabilizer, and the surfactant and stabilizer are added in no particular order.
  • the preparation method of the present disclosure may also include the steps of sterilizing and packaging the prepared pharmaceutical composition (for example, packaging into vials).
  • the present disclosure does not specifically limit the sterilization method, and membrane filtration may be selected but is not limited to it.
  • the buffer comprises a phosphate buffer, a histidine buffer, an acetate buffer and/or a citrate buffer.
  • the stabilizer comprises a sugar alcohol, a disaccharide, a monosaccharide, an amino acid and/or a salt.
  • the surfactant comprises a polysorbate, a poloxamer and/or a polyethylene glycol.
  • the present disclosure provides a method for treating a disease in a subject, the method comprising administering a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure provides a method for treating a disease in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a medicament for treating a disease in a subject.
  • the present disclosure provides a method for enhancing the immune response of a subject, the method comprising administering the pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure provides a method for enhancing the immune response of a subject, the method comprising administering a therapeutically effective amount of the pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a medicament for enhancing the immune response of a subject.
  • the present disclosure provides a method for inducing or enhancing an anti-tumor immune response, the method comprising administering a pharmaceutical composition or lyophilized preparation of the present disclosure to a subject.
  • the present disclosure provides a method for inducing or enhancing an anti-tumor immune response, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized preparation of the present disclosure to a subject.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a drug for inducing or enhancing an anti-tumor immune response.
  • the present disclosure provides a method for treating cancer in a subject, the method comprising administering a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure provides a method for treating cancer in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a medicament for treating cancer in a subject.
  • cancer is the name of a disease in which body cells become abnormal and divide and grow uncontrolled.
  • the cancer is a recurrent, refractory, metastatic, and/or advanced cancer.
  • the cancer is a non-solid tumor.
  • the cancer is a solid tumor.
  • the cancer includes but is not limited to head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcomas, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcomas, lymphomas, and hematologic tumors.
  • the head and neck cancer comprises head and neck squamous cell carcinoma.
  • the esophageal cancer comprises esophageal squamous cell carcinoma.
  • the lung cancer comprises small cell lung cancer and non-small cell lung cancer.
  • the liver cancer comprises hepatocellular carcinoma.
  • the kidney cancer comprises renal cell carcinoma.
  • the bladder cancer comprises urothelial carcinoma.
  • the skin cancer comprises melanoma.
  • the lymphoma includes Hodgkin lymphoma and non-Hodgkin lymphoma. In some embodiments, the lymphoma includes T-cell non-Hodgkin lymphoma or B-cell non-Hodgkin lymphoma.
  • the non-Hodgkin lymphoma includes primary Primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, marginal zone lymphoma, and/or AIDS-related B-cell lymphoma.
  • the blood stream includes myeloma, leukemia, myelodysplastic syndrome, myelofibrosis, and B-cell malignancies.
  • the leukemia includes acute lymphocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and chronic myelomonocytic leukemia.
  • compositions or lyophilized formulations of the present disclosure may be administered together with cancer therapeutic agents known in the art.
  • the present disclosure provides a method for treating an infectious disease of a subject, the method comprising administering a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure provides a method for treating an infectious disease of a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition or lyophilized preparation of the present disclosure to the subject.
  • the present disclosure also provides the use of the pharmaceutical composition and lyophilized preparation of the present disclosure in the preparation of a medicament for treating an infectious disease.
  • the infectious disease is a disease caused by organisms such as bacteria, fungi, parasites, viruses or other pathogens, including but not limited to AIDS, viral hepatitis, viral pneumonia, hand, foot and mouth disease, meningitis, measles, etc.
  • the pharmaceutical composition or lyophilized preparation of the present disclosure can be administered together with an infectious disease therapeutic agent known in the art, such as a vaccine.
  • compositions and lyophilized preparations disclosed herein can be administered according to methods known in the art.
  • the lyophilized preparations need to be reconstituted before administration to obtain a reconstituted solution of the lyophilized preparation.
  • reconstitution can be performed with water for injection, sodium chloride injection, Ringer's solution, or glucose injection.
  • compositions of the present disclosure and lyophilized preparations are suitable for parenteral administration.
  • pharmaceutical compositions of the present disclosure and lyophilized preparations are suitable for intravenous, intramuscular, intraperitoneal, subcutaneous, epidermal, spinal, intralesional injection or infusion.
  • pharmaceutical compositions of the present disclosure and lyophilized preparations are suitable for topical administration, inhalation, oral administration or administration by sustained release or delayed release delivery systems.
  • pharmaceutical compositions of the present disclosure, lyophilized preparations, and the reconstituted solution of lyophilized preparations can be diluted with a suitable diluent before administration.
  • water for injection, sodium chloride injection, Ringer's solution, or glucose injection can be diluted.
  • the present disclosure also provides a product, which includes a container, wherein the container contains a pharmaceutical composition or lyophilized preparation of the present disclosure.
  • the product of the present disclosure may also include instructions for the pharmaceutical composition or lyophilized preparation of the present disclosure for treating a disease.
  • the container is a single chamber (containing a pharmaceutical composition or lyophilized preparation comprising an anti-PD-1 antibody or its antigen-binding fragment and an anti-TIM-3 antibody or its antigen-binding fragment).
  • the present disclosure also provides a medicine box or vial, which contains the pharmaceutical composition or lyophilized preparation of the present disclosure.
  • the medicine box and vial of the present disclosure may also contain instructions for the pharmaceutical composition or lyophilized preparation of the present disclosure for treating a disease.
  • the vial is a single chamber (containing a pharmaceutical composition or lyophilized preparation comprising an anti-PD-1 antibody or its antigen-binding fragment and an anti-TIM-3 antibody or its antigen-binding fragment).
  • the present disclosure also provides a medical device comprising a pharmaceutical composition or lyophilized preparation of the present disclosure.
  • the medical device of the present disclosure may also include instructions for the pharmaceutical composition or lyophilized preparation of the present disclosure for treating a disease.
  • the medical device includes a syringe and an intravenous bag.
  • the syringe or intravenous bag is a single chamber (containing a pharmaceutical composition or lyophilized preparation comprising an anti-PD-1 antibody or its antigen-binding fragment and an anti-TIM-3 antibody or its antigen-binding fragment).
  • the disease includes cancer.
  • the cancer is recurrent, refractory, metastatic and/or advanced cancer.
  • the cancer is a non-solid tumor.
  • the cancer is a solid tumor.
  • the cancer includes but is not limited to head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcomas, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcomas, lymphomas and hematological tumors.
  • the head and neck cancer comprises head and neck squamous cell carcinoma.
  • the esophageal cancer comprises esophageal squamous cell carcinoma.
  • the lung cancer comprises small cell lung cancer and non-small cell lung cancer.
  • the liver cancer comprises hepatocellular carcinoma.
  • the kidney cancer comprises renal cell carcinoma.
  • the bladder cancer comprises urothelial carcinoma.
  • the skin cancer comprises melanoma.
  • the lymphoma includes Hodgkin lymphoma and non-Hodgkin lymphoma. In some embodiments, the lymphoma includes T-cell non-Hodgkin lymphoma or B-cell non-Hodgkin lymphoma.
  • the non-Hodgkin lymphoma includes primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, peripheral T-cell lymphoma, mantle cell lymphoma, primary B-cell lymphoma, Kitt's lymphoma, lymphoblastic lymphoma, cutaneous T-cell lymphoma, cutaneous B-cell lymphoma, marginal zone lymphoma, and/or AIDS-associated B-cell lymphoma.
  • the blood stream includes myeloma, leukemia, myelodysplastic syndrome, myelofibrosis, and B-cell malignancies.
  • the leukemia includes acute lymphocytic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and chronic myelomonocytic leukemia.
  • the disease includes an infectious disease.
  • the infectious disease is a disease caused by organisms such as bacteria, fungi, parasites, viruses or other pathogens, including but not limited to AIDS, viral hepatitis, viral pneumonia, hand, foot and mouth disease, meningitis, measles, etc.
  • the pharmaceutical composition of the present disclosure can be provided in any desired volume.
  • the pharmaceutical composition of the present disclosure is present in a single cavity of a container, vial, syringe or intravenous bag with a filling volume of 1 ml, 2 ml, 5 ml, 10 ml, or 20 ml.
  • the pharmaceutical composition of the present disclosure is present in a single cavity of a container, vial, syringe or intravenous bag with a filling volume of 30 ml or 40 ml.
  • the container, vial, syringe or intravenous bag contains 100 mg of anti-PD-1 antibody or its antigen-binding fragment and 600 mg of anti-TIM-3 antibody or its antigen-binding fragment.
  • Embodiment 1 A pharmaceutical composition comprising (a) an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof, (b) a buffer, (c) a stabilizer, and (d) a surfactant.
  • Embodiment 2 The pharmaceutical composition according to embodiment 1, wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-TIM-3 antibody or its antigen-binding fragment is 1:1-30, 1:1-20, 1:1-18, 1:1-15, 1:1-12, 1:1-10, 1:1-9, 1:1-7.5, 1:1-6, 1:1-5, 1:1-4.5, 1:1-3, 1:1-2 or 1:1-1.5.
  • Embodiment 3 The pharmaceutical composition according to embodiment 1 or 2, wherein the concentration of the anti-PD-1 antibody or its antigen-binding fragment is 1-100 mg/mL, 1-80 mg/mL, 2-60 mg/mL, 3-30 mg/mL, 3-20 mg/mL, 5-20 mg/mL, 5-15 mg/mL, or 5-10 mg/mL.
  • Embodiment 4 A pharmaceutical composition according to any one of Embodiments 1-3, wherein the concentration of the anti-TIM-3 antibody or its antigen-binding fragment is 1-200 mg/mL, 3-180 mg/mL, 6-120 mg/mL, 10-90 mg/mL, 15-90 mg/mL, 15-60 mg/mL, or 30-60 mg/mL.
  • Embodiment 5 The pharmaceutical composition according to any one of Embodiments 1 to 4, wherein the mass of the anti-PD-1 antibody or antigen-binding fragment thereof is 100-200 mg, or any multiple/fraction of a value within the range.
  • Embodiment 6 A pharmaceutical composition according to any one of Embodiments 1 to 5, wherein the mass of the anti-TIM-3 antibody or its antigen-binding fragment is 100-2400 mg, 100-1800 mg, 300-1800 mg, 600-1500 mg, or 600-1200 mg, or any multiple/fraction of a value within the range.
  • Embodiment 7 A pharmaceutical composition according to any one of Embodiments 1-6, wherein the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer and/or a citrate buffer.
  • the buffer comprises a histidine buffer, an acetate buffer, a Tris buffer, a phosphate buffer and/or a citrate buffer.
  • Embodiment 8 The pharmaceutical composition according to any one of embodiments 1-7, wherein the concentration of the buffer is 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM.
  • Embodiment 9 A pharmaceutical composition according to any one of embodiments 1-8, wherein the pharmaceutical composition comprises 1-100 mM, 2-80 mM, 5-60 mM, 10-40 mM, or 10-20 mM histidine buffer.
  • Embodiment 10 A pharmaceutical composition according to any one of embodiments 1-9, wherein the stabilizer comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof and/or sodium chloride.
  • the stabilizer comprises mannitol, sorbitol, trehalose, sucrose, maltose, lactose, lysine, glycine, proline, arginine or a pharmaceutically acceptable salt thereof and/or sodium chloride.
  • Embodiment 11 A pharmaceutical composition according to any one of embodiments 1-10, wherein the concentration of the stabilizer is 1-400 mg/mL, 10-300 mg/mL, 20-200 mg/mL, 40-200 mg/mL, 40-180 mg/mL, 60-180 mg/mL, or 70-170 mg/mL.
  • Embodiment 12 The pharmaceutical composition of any one of embodiments 1-11, wherein the pharmaceutical composition comprises 1-400 mg/mL, 10-300 mg/mL, 20-200 mg/mL, 40-200 mg/mL, 40-180 mg/mL, 60-180 mg/mL, or 70-170 mg/mL of sucrose.
  • Embodiment 13 The pharmaceutical composition according to any one of embodiments 1-12, wherein the surfactant comprises polysorbate 80 or polysorbate 20.
  • Embodiment 14 A pharmaceutical composition according to any one of Embodiments 1-13, wherein the concentration of the surfactant is 0.01-3 mg/mL, 0.04-2 mg/mL, 0.08-1.6 mg/mL, 0.1-1.2 mg/mL, 0.1-1 mg/mL, 0.2-0.8 mg/mL, or 0.4-0.8 mg/mL.
  • Embodiment 15 The pharmaceutical composition of any one of Embodiments 1-14, wherein the pharmaceutical composition comprises 0.01-3 mg/mL, 0.04-2 mg/mL, 0.08-1.6 mg/mL, 0.1-1.2 mg/mL, 0.1-1 mg/mL, 0.2-0.8 mg/mL, or 0.4-0.8 mg/mL of polysorbate 80.
  • Embodiment 16 The pharmaceutical composition of any one of Embodiments 1-15, wherein the pH of the pharmaceutical composition is 5 to 7, 5.5 to 7, 5.5 to 6.5, or 5.8 to 6.5.
  • Embodiment 17 The pharmaceutical composition according to any one of Embodiments 1-16, wherein the pharmaceutical composition comprises:
  • an anti-PD-1 antibody or an antigen-binding fragment thereof and an anti-TIM-3 antibody or an antigen-binding fragment thereof (b) 10-20 mM histidine buffer, (c) 60-180 mg/mL sucrose, and (d) 0.2-0.8 mg/mL polysorbate 80; wherein the fixed dose ratio of the anti-PD-1 antibody or its antigen-binding fragment to the anti-LAG-3 antibody or its antigen-binding fragment is 1:2, 1:3, 1:6 or 1:7.5, and the pH of the pharmaceutical composition is 5.5 to 6.5;
  • Embodiment 18 The pharmaceutical composition according to any one of Embodiments 1-17, wherein the pharmaceutical composition comprises:
  • Embodiment 19 The pharmaceutical composition according to any one of Embodiments 1 to 18, wherein the anti-PD-1 antibody or antigen-binding fragment thereof
  • the segment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:16.
  • Embodiment 20 A pharmaceutical composition according to any one of Embodiments 1-19, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18.
  • Embodiment 21 A pharmaceutical composition according to any one of Embodiments 1-20, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.
  • Embodiment 22 A pharmaceutical composition according to any one of Embodiments 1-21, wherein the anti-TIM-3 antibody or its antigen-binding fragment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6; or HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26.
  • Embodiment 23 A pharmaceutical composition according to any one of Embodiments 1-22, wherein the anti-TIM-3 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:7, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:8; or a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:27, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:28.
  • Embodiment 24 A pharmaceutical composition according to any one of Embodiments 1-23, wherein the anti-TIM-3 antibody or its antigen-binding fragment comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:9, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:10; or a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:29, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:30.
  • Embodiment 25 A lyophilized preparation, wherein the lyophilized agent is obtained by freeze-drying the pharmaceutical composition according to any one of Embodiments 1-24; or the lyophilized agent can form the pharmaceutical composition according to any one of Embodiments 1-24 after reconstitution.
  • Embodiment 26 A vial, wherein the vial contains the pharmaceutical composition of any one of Embodiments 1-24 or the lyophilized formulation of Embodiment 25.
  • Embodiment 27 Use of the pharmaceutical composition of any one of Embodiments 1-24 or the lyophilized formulation of Embodiment 25 in the preparation of a medicament for treating a disease in a subject.
  • Embodiment 28 The use according to Embodiment 27, wherein the disease comprises cancer and an infectious disease; optionally, the cancer is recurrent, refractory, metastatic and/or advanced cancer.
  • Embodiment 29 The use according to embodiment 28, wherein the cancer comprises head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, nervous system tumors, sarcoma, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcoma, lymphoma and hematological tumors.
  • head and neck cancer nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder
  • Embodiment 30 The use according to any one of embodiments 27 to 29, wherein the pharmaceutical composition or lyophilized preparation is suitable for parenteral administration.
  • Embodiment 31 A method of treating a disease in a subject, the method comprising administering to the subject the pharmaceutical composition of any one of Embodiments 1-24 or the lyophilized formulation of Embodiment 25.
  • Embodiment 32 The method according to embodiment 31, wherein the disease includes cancer and an infectious disease; optionally, the cancer is recurrent, refractory, metastatic and/or advanced cancer.
  • Embodiment 33 The method according to embodiment 32, wherein the cancer comprises head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer, glioblastoma, bladder cancer, breast cancer, ovarian cancer, fallopian tube cancer, prostate cancer, anal cancer, testicular cancer, vaginal cancer, gastric cancer, gastroesophageal junction cancer, pancreatic cancer, bone cancer, thyroid cancer, skin cancer, Skin cancer, nervous system tumors, sarcomas, myeloma, bile duct cancer, gallbladder cancer, soft tissue sarcomas, lymphomas and hematological tumors.
  • the cancer comprises head and neck cancer, nasopharyngeal cancer, oral cancer, esophageal cancer, lung cancer, liver cancer, colon cancer, colorectal cancer, kidney cancer, endometrial cancer, cervical cancer,
  • Embodiment 34 The method according to any one of embodiments 31-33, wherein the pharmaceutical composition or lyophilized formulation is suitable for parenteral administration.
  • Embodiment 35 The method according to any one of embodiments 31-34, wherein the pharmaceutical composition or lyophilized formulation is administered to the subject in a therapeutically effective amount.
  • the heavy chain amino acid sequence of the anti-TIM-3 antibody h50B5 in the embodiment is shown in SEQ ID NO: 9 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO: 10 of the present disclosure.
  • the heavy chain amino acid sequence of the anti-PD-1 antibody 14C12H1L1 in the embodiment is shown in SEQ ID NO: 19 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO: 20 of the present disclosure.
  • the heavy chain amino acid sequence of TSR022 in the embodiment is shown in SEQ ID NO: 32, and the light chain amino acid sequence is shown in SEQ ID NO: 33.
  • Human TIM-3 (R&D) recombinant protein was coated in ELISA 96-well plates (Greiner), and different concentrations of anti-TIM-3 antibody h50B5 (100000 ng/mL, 30000 ng/mL, 10000 ng/mL, 3000 ng/mL, 1000 ng/mL, 300 ng/mL, 100 ng/mL, 30 ng/mL, 100 ng/mL, 30 ng/mL, 10 ng/mL, 3 ng/mL) were added and incubated at 37°C for 1 hour.
  • anti-TIM-3 antibody h50B5 100000 ng/mL, 30000 ng/mL, 10000 ng/mL, 3000 ng/mL, 1000 ng/mL, 300 ng/mL, 100 ng/mL, 30 ng/mL, 100 ng/mL, 30 ng/mL, 10 ng/mL, 3 ng/mL
  • the anti-TIM-3 antibody h50B5 had a strong binding affinity to the human TIM-3 protein, with a binding EC 50 of 291.0 ⁇ 14.1 ng/mL and a maximum binding E max (OD 450 ) of 0.52 ⁇ 0.03.
  • the human TIM-3 gene was transfected into CHO-S cells and cultured in Dynamis AGT culture medium (containing 4 mM glutamate and 3 ⁇ g/mL Puromycin) at 37° C. in an incubator containing 5% CO 2 in air to obtain CHO-S-HuTIM-3 cells.
  • Dynamis AGT culture medium containing 4 mM glutamate and 3 ⁇ g/mL Puromycin
  • h50B5 or TSR022 Different concentrations of h50B5 or TSR022 (300000ng/mL, 100000ng/mL, 30000ng/mL, 10000ng/mL, 3000ng/mL, 1000ng/mL, 300ng/mL, 1000ng/mL, 300ng/mL, 100ng/mL, 30ng/mL, 10ng/mL) were incubated with CHO-S-HuTIM-3 cells at 4°C for 1 hour, and then Goat anti-human Ig kappa chain-HRP conjugate was added and incubated at 37°C for 1 hour. Finally, HRP substrate OPD was added, and the reaction was terminated with H2SO4 . The OD value was measured at a wavelength of 450nm using a full-function microplate reader Synergy H4. The binding EC50 was calculated based on the OD value.
  • h50B5 binds strongly to CHO-S-HuTIM-3 cells that highly express human TIM-3, with EC 50 and maximum binding E max (OD 450 ) of 1456.0 ⁇ 338.0 ng/mL and 0.21 ⁇ 0.03, respectively; the EC 50 and maximum binding E max (OD 450 ) of TSR022 binding to CHO-S-HuTIM-3 cells are 6815.5 ⁇ 166.2 ng/mL and 0.26 ⁇ 0.05, respectively, indicating that the binding activity of h50B5 is stronger than that of TSR022.
  • CD14 + monocytes were isolated from human PBMC (prepared in-house) using a CD14 magnetic bead sorting kit (Miltenyi Biotec), and then induced with GM-CSF (Xiamen Tebao Bioengineering Co., Ltd.) for 7 days to differentiate into mature dendritic cells (DC); CD4 + T cells were isolated from human PBMC using a CD4 + T cell magnetic bead sorting kit (Miltenyi Biotec), and then CD4 + T cells were mixed with mature DC cells, and different concentrations of h50B5 or TSR022 (100 ⁇ g/mL, 10 ⁇ g/mL, 1 ⁇ g/mL) were added, and a blank control (no antibody) was set up and incubated for 5 days. After the incubation, the supernatant was aspirated and the IFN- ⁇ content in the supernatant was detected using an IFN- ⁇ detection kit (Cisbio).
  • NCG mice were subcutaneously inoculated with HCC827 cells (Cell Bank of the Chinese Academy of Sciences), 8 ⁇ 10 6 cells/mouse.
  • human PBMC Shanghai Ausells Biotechnology (Shanghai) Co., Ltd., catalog number PB004F
  • PB004F human PBMC
  • h50B5 or hIgG4 dosage was 10 mg/kg
  • TILs TILs
  • Histidine-histidine hydrochloride buffer prepared from L-histidine and histidine hydrochloride monohydrate.
  • 20mM histidine-histidine hydrochloride buffer pH 6.0
  • Acetic acid-sodium acetate buffer prepared from acetic acid and sodium acetate trihydrate.
  • 20 mM acetic acid-sodium acetate buffer pH 6.0
  • 20 mM acetic acid-sodium acetate buffer pH 6.0
  • Histidine-HCl buffer prepared with L-histidine and adjusted to the target pH with hydrochloric acid.
  • 20 mM histidine-HCl buffer pH 5.8 can be prepared with about 3.1 g/L L-histidine and adjusted to pH 5.8 with hydrochloric acid.
  • Histidine-acetate buffer prepared with L-histidine and adjusted to the target pH with acetic acid.
  • 20 mM histidine-acetate buffer pH 5.8 can be prepared with about 3.1 g/L L-histidine and adjusted to pH 5.8 with acetic acid.
  • Size exclusion chromatography (SEC-UPLC): used to determine the purity of antibodies in samples, using Thermo Vanquish F high performance liquid chromatography, ACQUITY UPLC Protein BEH SEC Column ( 1.7 ⁇ m,4.6*300mm) as the chromatographic column, ACQUITY UPLC Protein BEH SEC Guard Column( 1.7 ⁇ m, 4.6*30mm) as pre-column, 50mmol/L phosphate-200mmol/L sodium chloride solution (pH 7.0) as mobile phase for elution, and the detection wavelength was 280nm. The peak area percentages of high molecular impurities and immunoglobulin monomers were calculated by area normalization method.
  • Unfolding temperature (Tm) MicroCal VP-Capillary DSC (Malvern) was used to analyze the unfolding temperature (Tm) of the samples. The samples were diluted to a concentration of 1 mg/mL. The procedure was as follows: the scan start temperature was 20°C, the scan end temperature was 110°C, and the heating rate was 60°C/h.
  • TIM-3 protein (ACRO, TM3-H5229) was coated in a 96-well plate, 100 ⁇ L/well, and incubated at 2-8°C overnight. After washing the 96-well plate, 250 ⁇ L of blocking solution (PBS solution containing 3% BSA) was added to each well and incubated at 25°C for 2 hours.
  • ELISA enzyme-linked immunosorbent assay
  • Test sample biological activity (%) (reference sample EC 50 value/test sample EC 50 value) ⁇ 100%.
  • the binding activity with PD-1 was detected by enzyme-linked immunosorbent assay (ELISA): 2 ⁇ g/mL PD-1 protein (Sinobiological, 10377-H08H) was coated in a 96-well plate, 100 ⁇ L/well, and incubated at 2-8°C overnight. After washing the 96-well plate, 250 ⁇ L of blocking solution (PBS solution containing 3% BSA) was added to each well and incubated at 25°C for 2 hours.
  • ELISA enzyme-linked immunosorbent assay
  • Test sample biological activity (%) (reference sample EC 50 value/test sample EC 50 value) ⁇ 100%.
  • DLS Dynamic light scattering
  • the anti-TIM-3 antibody h50B5 was replaced into the buffer in Table 3-1 by ultrafiltration, and concentrated after the replacement, and then the surfactant and stabilizer were added according to Table 3-1 to obtain the h50B5 stock solution.
  • the anti-PD-1 antibody 14C12H1L1 was replaced into the buffer in Table 3-1, and then the 14C12H1L1 stock solution was prepared in the same way.
  • the h50B5 stock solution and the 14C12H1L1 stock solution were mixed evenly according to the proportion to obtain a pharmaceutical composition, wherein the concentration of h50B5 in the pharmaceutical composition was 60 mg/mL and the concentration of 14C12H1L1 was 10 mg/mL.
  • the pharmaceutical composition was sterilized by filtering through a 0.22 ⁇ m filter membrane, and dispensed into a vial, stoppered and capped.
  • the pharmaceutical composition shown in Table 3-1 was subjected to Tm and Tagg tests, and the test results are shown in Table 3-2. The results show that the pharmaceutical composition has good conformational stability and colloidal stability in the pH range of 5.5-7.0.
  • the pharmaceutical composition shown in Table 3-1 was placed at 40°C for 1 month and 2-8°C for 1 month, and the SEC-UPLC test results are shown in Table 3-3.
  • the anti-TIM-3 antibody h50B5 was replaced into the buffer in Table 4-1 by ultrafiltration, and concentrated after the replacement, and then the surfactant and stabilizer were added according to Table 4-1 to obtain the h50B5 stock solution.
  • the anti-PD-1 antibody 14C12H1L1 was replaced into the buffer in Table 4-1, and then the 14C12H1L1 stock solution was prepared in the same way.
  • the h50B5 stock solution and the 14C12H1L1 stock solution were mixed evenly according to the proportion to obtain a pharmaceutical composition, wherein the concentration of h50B5 in the pharmaceutical composition was 30 mg/mL and the concentration of 14C12H1L1 was 5 mg/mL.
  • the pharmaceutical composition was sterilized by filtration through a 0.22 ⁇ m filter membrane, and dispensed into vials, stoppered and capped.
  • the drug composition shown in Table 4-1 was subjected to Tm and Tagg detection, and the detection results are shown in Table 4-2. The results show that the Tagg value of drug composition F5 is the lowest.
  • the drug composition shown in Table 4-1 was placed at 40°C for 1 month, 25°C for 1 month, and 2-8°C for 1 month, and the SEC-UPLC detection results are shown in Table 4-3.
  • the anti-TIM-3 antibody h50B5 was replaced into the buffer in Table 5-1 by ultrafiltration, and concentrated after the replacement, and then the surfactant and stabilizer were added according to Table 5-1 to obtain the h50B5 stock solution.
  • the anti-PD-1 antibody 14C12H1L1 was replaced into the buffer in Table 5-1, and then the 14C12H1L1 stock solution was prepared in the same way.
  • the h50B5 stock solution and the 14C12H1L1 stock solution were mixed evenly according to the proportion to obtain a pharmaceutical composition, wherein the concentration of h50B5 in the pharmaceutical composition was 30 mg/mL and the concentration of 14C12H1L1 was 5 mg/mL.
  • the pharmaceutical composition was sterilized by filtering through a 0.22 ⁇ m filter membrane, and dispensed into vials, stoppered and capped.
  • the pharmaceutical composition shown in Table 5-1 was placed at 40°C for 1 month, 25°C for 1 month, and 2-8°C for 1 month.
  • the SEC-UPLC test results are shown in Table 5-2, and the DLS particle size and binding activity test results are shown in Table 5-4.
  • the pharmaceutical composition shown in Table 5-1 was shaken at 25°C for 5 days and 25°C for 10 days, and the SEC-UPLC test results are shown in Table 5-3.
  • the results show that the pharmaceutical composition maintains good stability when the sucrose concentration is in the range of 80 mg/mL to 164.3 mg/mL and the polysorbate 80 concentration is in the range of 0.4 mg/mL to 0.8 mg/mL.
  • the anti-TIM-3 antibody h50B5 was replaced into the buffer in Table 6-1 by ultrafiltration, and concentrated after the replacement, and then the surfactant and stabilizer were added according to Table 6-1 to obtain the h50B5 stock solution.
  • the anti-PD-1 antibody 14C12H1L1 was replaced into the buffer in Table 6-1, and then the 14C12H1L1 stock solution was prepared in the same way.
  • a blank stock solution without antibody was prepared by adding a buffer, a surfactant and a stabilizer according to Table 6-1.
  • the h50B5 stock solution, the 14C12H1L1 stock solution and the blank stock solution were mixed evenly in proportion to obtain a pharmaceutical composition, wherein the concentration of h50B5 in the pharmaceutical composition was 15 mg/mL and the concentration of 14C12H1L1 was 5 mg/mL.
  • the pharmaceutical composition was sterilized by filtration through a 0.22 ⁇ m filter membrane, and dispensed into a vial, stoppered and capped.
  • the pharmaceutical composition shown in Table 6-1 was placed at 40°C for 1 month, 25°C for 1 month, and 2-8°C for 1 month, respectively.
  • the SEC-UPLC test results are shown in Table 6-2.

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Abstract

La présente invention appartient au domaine de la biomédecine, et concerne une composition pharmaceutique comprenant un anticorps anti-PD-1 et un second anticorps, le second anticorps étant un anticorps anti-TIM-3. De plus, la présente invention concerne également un procédé de préparation de la composition pharmaceutique et l'utilisation de la composition pharmaceutique dans la préparation d'un médicament pour le traitement de maladies chez un sujet.
PCT/CN2024/118679 2023-09-13 2024-09-13 Composition pharmaceutique comprenant un anticorps anti-pd-1 et un second anticorps Pending WO2025056014A1 (fr)

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Citations (6)

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Publication number Priority date Publication date Assignee Title
CN106977602A (zh) * 2016-08-23 2017-07-25 中山康方生物医药有限公司 一种抗 pd1 单克隆抗体、其药物组合物及其用途
CN112566936A (zh) * 2018-08-21 2021-03-26 阿尔伯特爱因斯坦医学院 针对人tim-3的单克隆抗体
CN116710071A (zh) * 2020-12-28 2023-09-05 百时美施贵宝公司 Pd1/pd-l1抗体的皮下施用
WO2023217268A1 (fr) * 2022-05-13 2023-11-16 正大天晴药业集团南京顺欣制药有限公司 Combinaison médicamenteuse d'anticorps anti-tim-3 et d'anticorps anti-pd-1
WO2024051670A1 (fr) * 2022-09-06 2024-03-14 正大天晴药业集团股份有限公司 Combinaison pharmaceutique d'anticorps se liant à tim-3 et d'anticorps se liant à pd-1
WO2024183643A1 (fr) * 2023-03-03 2024-09-12 正大天晴药业集团南京顺欣制药有限公司 Combinaison pharmaceutique contenant un anticorps anti-tim-3

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CN106977602A (zh) * 2016-08-23 2017-07-25 中山康方生物医药有限公司 一种抗 pd1 单克隆抗体、其药物组合物及其用途
CN112566936A (zh) * 2018-08-21 2021-03-26 阿尔伯特爱因斯坦医学院 针对人tim-3的单克隆抗体
CN116710071A (zh) * 2020-12-28 2023-09-05 百时美施贵宝公司 Pd1/pd-l1抗体的皮下施用
WO2023217268A1 (fr) * 2022-05-13 2023-11-16 正大天晴药业集团南京顺欣制药有限公司 Combinaison médicamenteuse d'anticorps anti-tim-3 et d'anticorps anti-pd-1
WO2024051670A1 (fr) * 2022-09-06 2024-03-14 正大天晴药业集团股份有限公司 Combinaison pharmaceutique d'anticorps se liant à tim-3 et d'anticorps se liant à pd-1
WO2024183643A1 (fr) * 2023-03-03 2024-09-12 正大天晴药业集团南京顺欣制药有限公司 Combinaison pharmaceutique contenant un anticorps anti-tim-3

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Title
CURIGLIANO, G. ET AL.: "Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors", CLINICAL CANCER RESEARCH, vol. 27, no. 13, 21 April 2021 (2021-04-21), pages 3620 - 3629, XP093005120, DOI: 10.1158/1078-0432.CCR-20-4746 *

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